New Data from Bristol-Myers Squibb Oncology Portfolio to be Presented at 2011 American Society of Clinical Oncology (ASCO)

  • Results from Second Phase 3 Study of YERVOY™ (ipilimumab) in Patients with Metastatic Melanoma Selected for ASCO Plenary Session
  • Investigational Uses of Currently-Approved Products and Investigational Compounds to be Featured in More than 95 Abstracts
  • Data Spans Broad Range of Therapeutic Approaches and More Than 15 Tumor Types

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE:BMY), a leading global BioPharma company in oncology, today announced that more than 95 scientific abstracts on its approved and investigational oncology compounds will be featured at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago from June 3-7. In a separate release, the company also announced that YERVOY™ (ipilimumab) received a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) in Europe for the treatment of patients with previously-treated unresectable or metastatic melanoma.

New data from YERVOY, a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody, will be highlighted at the meeting, including:

  • Results from a second Phase 3 study of YERVOY in patients with metastatic melanoma, which have been selected for presentation in the plenary session at ASCO on Sunday, June 5.
  • Survival and safety data from a separate study investigating YERVOY in metastatic melanoma patients with stable asymptomatic brain metastases.
  • Data from a clinical trial describing the response to YERVOY in patients with metastatic melanoma according to their baseline BRAF status.

“The presentations at ASCO reflect our broad commitment to oncology and, specifically, the science of immuno-oncology, a key area of research at Bristol-Myers Squibb that focuses on leveraging the potential of the immune system’s intrinsic ability to fight cancer,” said Elliott Sigal, M.D., Ph.D., executive vice president, chief scientific officer and president, Research and Development, Bristol-Myers Squibb. “With the recent FDA approval of YERVOY, today’s CHMP positive opinion and additional clinical trial results, our R&D group is gaining momentum in the exploration of our various compounds’ potential in a broad range of cancers.”

Other Key Oncology Asset News

Bristol-Myers Squibb and its partner, Abbott, will present updated Phase 1 and 2 results on elotuzumab, which is under development for the treatment of multiple myeloma. Elotuzumab is an investigational humanized monoclonal antibody specifically targeted against CS1, a cell-surface glycoprotein that is highly and uniformly expressed on multiple myeloma cells. On Sunday, June 5, updated results evaluating the safety and efficacy of elotuzumab plus lenalidomide and low-dose dexamethasone in patients with relapsed multiple myeloma will be presented during an oral session. A Phase 3 clinical trial for elotuzumab in relapsed multiple myeloma was recently initiated and is now actively recruiting patients.

Separately, the company and its partner, Otsuka Pharmaceutical Co., Ltd., will present two-year follow up data from the Phase 3 head-to-head trial known as DASISION evaluating SPRYCEL® (dasatinib) vs. Gleevec®* (imatinib mesylate) in the treatment of patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic-phase. Five-year data from the Phase 3 study (-034) that evaluated the safety and efficacy of SPRYCEL in the treatment of Ph+ CML patients with resistance or intolerance to Gleevec will also be presented. Both sets of results will be presented on Friday, June 3.

ERBITUX ® (cetuximab) will be highlighted in abstracts that span a wide range of investigational uses in solid tumors such as colorectal, lung and head and neck. On Saturday, June 4, ERBITUX data evaluating the influence of KRAS G13D mutations on outcome in patients with metastatic colorectal cancer will be featured in an oral presentation. Bristol-Myers Squibb is developing ERBITUX in partnership with Lilly.

IXEMPRA® (ixabepilone) will be featured in abstracts reporting results in combination regimens with other chemotherapies or targeted agents in different stages of breast cancer and results in different subgroups.

Other investigational compounds from the Bristol-Myers Squibb oncology portfolio will be presented, including Phase 2 advanced solid tumor data on brivanib, a selective dual inhibitor of FGF and VEGF signaling. On Monday, June 6, Phase 2 brivanib data in advanced soft tissue sarcoma will also be presented. BMS 754807 (a dual IGF-1R/IR inhibitor) and BMS 833293 (an SMO antagonist) will also be featured at ASCO.

YERVOY™ (ipilimumab) INDICATIONS & IMPORTANT SAFETY INFORMATION

YERVOY is indicated for the treatment of unresectable or metastatic melanoma.

Important Safety Information

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions due to T-cell activation and proliferation. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs) and thyroid function tests at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Recommended Dose Modifications

Withhold dose for moderate immune-mediated adverse reactions until return to baseline, improvement to mild severity, or complete resolution, and patient is receiving <7.5 mg prednisone or equivalent per day.

Permanently discontinue YERVOY for any of the following:

  • Persistent moderate adverse reactions or inability to reduce corticosteroid dose to 7.5 mg prednisone or equivalent per day.
  • Failure to complete full treatment course within 16 weeks from administration of first dose.
  • Severe or life-threatening adverse reactions.

Immune-mediated Enterocolitis:

  • In the pivotal Phase 3 study in YERVOY-treated patients, severe, life-threatening or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) and moderate (diarrhea with up to 6 stools above baseline, abdominal pain, mucus or blood in stool; Grade 2) enterocolitis occurred in 28 (5%) patients.
  • Across all YERVOY-treated patients (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.
  • Monitor patients for signs and symptoms of enterocolitis (such as diarrhea, abdominal pain, mucus or blood in stool, with or without fever) and of bowel perforation (such as peritoneal signs and ileus).
    • In symptomatic patients, rule out infectious etiologies and consider endoscopic evaluation for persistent or severe symptoms.

Immune-mediated Hepatitis:

  • In the pivotal Phase 3 study in YERVOY-treated patients, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5X the upper limit of normal (ULN) or total bilirubin elevations >3X the ULN; Grade 3–5) occurred in 8 (2%), with fatal hepatic failure in 0.2% and hospitalization in 0.4%.
  • 13 (2.5%) additional YERVOY-treated patients experienced moderate hepatotoxicity manifested by LFT abnormalities (AST or ALT elevations >2.5X but ≤5X the ULN or total bilirubin elevation >1.5X but ≤3X the ULN; Grade 2).
  • Monitor LFTs (hepatic transaminase and bilirubin levels) and assess patients for signs and symptoms of hepatotoxicity before each dose of YERVOY.
    • In patients with hepatotoxicity, rule out infectious or malignant causes and increase frequency of LFT monitoring until resolution.

Immune-mediated Dermatitis:

  • In the pivotal Phase 3 study in YERVOY-treated patients, severe, life-threatening or fatal immune-mediated dermatitis (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3–5) occurred in 13 (2.5%) patients.
    • 1 (0.2%) patient died as a result of toxic epidermal necrolysis.
    • 1 additional patient required hospitalization for severe dermatitis.
  • There were 63 (12%) YERVOY-treated patients with moderate (Grade 2) dermatitis.
  • Monitor patients for signs and symptoms of dermatitis such as rash and pruritus. Unless an alternate etiology has been identified, signs or symptoms of dermatitis should be considered immune-mediated.

Immune-mediated Neuropathies:

  • In the pivotal Phase 3 study in YERVOY-treated patients, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.
  • Across the clinical development program of YERVOY, myasthenia gravis and additional cases of Guillain-Barré syndrome have been reported.
  • Monitor for symptoms of motor or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, or paresthesia.

Immune-Mediated Endocrinopathies:

  • In the pivotal Phase 3 study in YERVOY- treated patients, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%).
    • All 9 patients had hypopituitarism and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism.
    • 6 of the 9 patients were hospitalized for severe endocrinopathies.
  • Moderate endocrinopathy (requiring hormone replacement or medical intervention; Grade 2) occurred in 12 (2.3%) YERVOY-treated patients and consisted of hypothyroidism, adrenal insufficiency, hypopituitarism, and 1 case each of hyperthyroidism and Cushing’s syndrome.
  • Median time to onset of moderate to severe immune-mediated endocrinopathy was 11 weeks and ranged up to 19.3 weeks after the initiation of YERVOY.
  • Monitor patients for clinical signs and symptoms of hypophysitis, adrenal insufficiency (including adrenal crisis), and hyper- or hypothyroidism.
    • Patients may present with fatigue, headache, mental status changes, abdominal pain, unusual bowel habits, and hypotension, or nonspecific symptoms which may resemble other causes such as brain metastasis or underlying disease.
    • Unless an alternate etiology has been identified, signs or symptoms of endocrinopathies should be considered immune-mediated.
    • Monitor thyroid function tests and clinical chemistries at the start of treatment, before each dose, and as clinically indicated based on symptoms.
    • In a limited number of patients, hypophysitis was diagnosed by imaging studies through enlargement of the pituitary gland.

Other Immune-mediated Adverse Reactions, Including Ocular Manifestations:

  • In the pivotal Phase 3 study in YERVOY-treated patients, clinically significant immune-mediated adverse reactions seen in <1% were: nephritis, pneumonitis, meningitis, pericarditis, uveitis, iritis, and hemolytic anemia.
  • Across the clinical development program for YERVOY, immune-mediated adverse reactions also reported with <1% incidence were: myocarditis, angiopathy, temporal arteritis, vasculitis, polymyalgia rheumatica, conjunctivitis, blepharitis, episcleritis, scleritis, leukocytoclastic vasculitis, erythema multiforme, psoriasis, pancreatitis, arthritis, and autoimmune thyroiditis.

Pregnancy & Nursing:

  • YERVOY is classified as pregnancy category C. There are no adequate and well-controlled studies of YERVOY in pregnant women. Use YERVOY during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Human IgG1 is known to cross the placental barrier and YERVOY is an IgG1; therefore, YERVOY has the potential to be transmitted from the mother to the developing fetus.
  • It is not known whether YERVOY is secreted in human milk. Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from YERVOY, a decision should be made whether to discontinue nursing or to discontinue YERVOY.

Common Adverse Reactions:

  • The most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Please see full Prescribing Information, including Boxed WARNING regarding immune-mediated adverse reactions available at www.bms.com.

SPRYCEL® (dasatinib) INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATIONS

SPRYCEL® (dasatinib) is indicated for the treatment of adults with:

  • Newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The effectiveness of SPRYCEL is based on cytogenetic and major molecular response rates. The trial is ongoing and further data will be required to determine long-term outcome
  • Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
  • Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy

IMPORTANT SAFETY INFORMATION

Myelosuppression:

  • Treatment with SPRYCEL® (dasatinib) can cause severe (NCI CTC Grade 3/4) thrombocytopenia, neutropenia, and anemia, occurring more frequently in advanced phase CML or Ph+ ALL than in chronic phase CML. Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities
    • Perform complete blood counts (CBCs) weekly for the first 2 months and then monthly thereafter, or as clinically indicated
    • Myelosuppression was generally reversible and usually managed by dose interruption, dose reduction, or discontinuation
    • Hematopoietic growth factor has been used in patients with resistant myelosuppression

Bleeding Related Events:

  • SPRYCEL(dasatinib) caused platelet dysfunction in vitro and thrombocytopenia in humans
    • In all clinical trials, severe central nervous system (CNS) hemorrhage, including fatalities, occurred in 1% of patients. Severe gastrointestinal (GI) hemorrhage, including fatalities, occurred in 4% of patients receiving SPRYCEL, which generally required treatment interruptions and transfusions. Other cases of severe hemorrhage occurred in 2% of patients
  • Most bleeding events were associated with severe thrombocytopenia
    • Exercise caution in patients required to take medications that inhibit platelet function or anticoagulants

Fluid Retention:

  • SPRYCEL is associated with fluid retention
    • In clinical trials fluid retention was severe in up to 10% of patients. Ascites (<1%), generalized edema (<1%), and severe pulmonary edema (1%) were also reported
  • Patients who develop symptoms suggestive of pleural effusion such as dyspnea or dry cough should be evaluated by chest X-ray
  • Severe pleural effusion may require thoracentesis and oxygen therapy
  • Fluid retention was typically managed by supportive care measures that included diuretics or short courses of steroids

QT Prolongation:

  • In vitro data suggest that SPRYCEL (dasatinib) has the potential to prolong cardiac ventricular repolarization (QT interval)
  • In 865 patients with leukemia treated with SPRYCEL in five phase 2 single-arm studies, the maximum mean changes in QTcF (90% upper bound CI) from baseline ranged from 7.0 ms to 13.4 ms
  • In clinical trials of CML patients treated with SPRYCEL (N=2440), 15 patients (<1%) had QTc prolongation as an adverse reaction. Twenty-two patients (1%) experienced a QTcF >500 ms
  • Administer SPRYCEL with caution to patients who have or may develop prolongation of QTc, including patients with hypokalemia, hypomagnesemia, or congenital long QT syndrome and patients taking anti-arrhythmic drugs, other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy
    • Correct hypokalemia or hypomagnesemia prior to SPRYCEL administration

Congestive Heart Failure, Left Ventricular Dysfunction, and Myocardial Infarction:

Cardiac adverse reactions were reported in 5.8% of 258 patients taking SPRYCEL, including 1.6% of patients with cardiomyopathy, heart failure congestive, diastolic dysfunction, fatal myocardial infarction, and left ventricular dysfunction. Monitor patients for signs or symptoms consistent with cardiac dysfunction and treat appropriately.

Pregnancy:

SPRYCEL (dasatinib) may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of SPRYCEL in pregnant women. Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant when taking SPRYCEL.

Nursing Mothers:

It is unknown whether SPRYCEL is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue SPRYCEL.

Drug Interactions:

SPRYCEL is a CYP3A4 substrate and a weak time-dependent inhibitor of CYP3A4

  • Drugs that may increase SPRYCEL plasma concentrations are:
    • CYP3A4 inhibitors: Concomitant use of SPRYCEL and drugs that inhibit CYP3A4 should be avoided. If administration of a potent CYP3A4 inhibitor cannot be avoided, close monitoring for toxicity and a SPRYCEL dose reduction or temporary discontinuation should be considered
      • Strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). If SPRYCEL must be administered with a strong CYP3A4 inhibitor, a dose decrease should be considered
      • Grapefruit juice may also increase plasma concentrations of SPRYCEL and should be avoided
  • Drugs that may decrease SPRYCEL plasma concentrations are:
    • CYP3A4 inducers: If SPRYCEL must be administered with a CYP3A4 inducer, a dose increase in SPRYCEL should be considered.
      • Strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital), should be avoided. Alternative agents with less enzyme induction potential should be considered. If the dose of SPRYCEL is increased, the patient should be monitored carefully for toxicity
      • St John’s Wort may decrease SPRYCEL plasma concentrations unpredictably and should be avoided
    • Antacids. Antacids may decrease SPRYCEL drug levels. Simultaneous administration of SPRYCEL and antacids should be avoided. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of SPRYCEL
    • H2 antagonists/proton pump inhibitors, such as famotidine and omeprazole. Long-term suppression of gastric acid secretion by use of H2 antagonists or proton pump inhibitors is likely to reduce SPRYCEL exposure. Therefore, concomitant use of H2 antagonists or proton pump inhibitors with SPRYCEL is not recommended
  • Drugs that may have their plasma concentration altered by SPRYCEL are:
    • CYP3A4 substrates such as simvastatin. CYP3A4 substrates with a narrow therapeutic index should be administered with caution in patients receiving SPRYCEL

Adverse Reactions:

The safety data reflect exposure to SPRYCEL (dasatinib) in 258 patients with newly diagnosed chronic phase CML in a clinical study (median duration of therapy was 18 months) and in 2182 patients with imatinib resistant or intolerant CML or Ph+ ALL in clinical studies (minimum of 2 years follow-up).

The majority of SPRYCEL-treated patients experienced adverse reactions at some time. Patients aged 65 years and older are more likely to experience toxicity. In the newly diagnosed chronic phase CML study, SPRYCEL was discontinued for adverse reactions in 6% of patients. In patients resistant or intolerant to prior imatinib therapy, SPRYCEL was discontinued for adverse reactions in 15% patients in chronic phase, 16% in accelerated phase, 15% in myeloid blast phase, 8% in lymphoid blast phase CML, and 8% in Ph+ ALL.

  • In newly diagnosed chronic phase CML patients:
    • The most frequently reported serious adverse reactions included pleural effusion (2%), hemorrhage (2%), congestive heart failure (1%), and pyrexia (1%)
    • The most frequently reported adverse reactions (reported in ≥10% of patients) included myelosuppression, fluid retention events (pleural effusion, superficial localized edema,generalized edema), diarrhea, headache, musculoskeletal pain, and rash
    • Grade 3/4 laboratory abnormalities included neutropenia (22%), thrombocytopenia (19%), anemia (11%), and hypophosphatemia (5%), hypocalcemia (3%), and elevated bilirubin (1%)
  • In patients resistant or intolerant to prior imatinib therapy:
    • The most frequently reported serious adverse reactions included pleural effusion (11%), gastrointestinal bleeding (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), infection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%), and CNS hemorrhage (1%)
    • The most frequently reported adverse reactions (reported in ≥20% of patients) included myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage
    • Grade 3/4 laboratory abnormalities in chronic phase CML patients resistant or intolerant to prior imatinib therapy who received SPRYCEL 100 mg once daily included neutropenia (36%), thrombocytopenia (23%), anemia (13%), hypophosphatemia (10%), and hypokalemia (2%)
  • Grade 3/4 elevations of transaminase or bilirubin and Grade 3/4 hypocalcemia, hypokalemia and hypophosphatemia were reported in patients with all phases of CML, but were reported with an increased frequency in patients with myeloid or lymphoid blast phase CML
    • Elevations in transaminase or bilirubin were usually managed with dose reduction or interruption
    • Patients developing Grade 3/4 hypocalcemia during the course of SPRYCEL therapy often had recovery with oral calcium supplementation

The full Prescribing Information is available at www.bms.com.

IXEMPRA (ixabepilone) INDICATIONS & IMPORTANT SAFETY INFORMATION
INDICATIONS AND USAGE

IXEMPRA (ixabepilone) is indicated in combination with capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated. Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant setting or 3 months in the metastatic setting. Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant setting or 4 months in the metastatic setting.

IXEMPRA is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine.

Important Safety Information

Toxicity in hepatic impairment

-IXEMPRA (ixabepilone) in combination with capecitabine is contraindicated in patients with AST or ALT >2.5 × ULN or bilirubin >1 × ULN due to increased risk of toxicity and neutropenia-related death

-In combination with capecitabine, the overall frequency of grade 3/4 adverse reactions, febrile neutropenia, serious adverse reactions, and toxicity-related deaths was greater in patients with hepatic impairment

-Caution should be used when using IXEMPRA as monotherapy in patients with AST or ALT >5 × ULN. Use of IXEMPRA in patients with AST or ALT >10 × ULN or bilirubin >3 × ULN is not recommended

-With monotherapy, grade 4 neutropenia, febrile neutropenia, and serious adverse reactions were more frequent in patients with hepatic impairment

Contraindications

-IXEMPRA is contraindicated in patients:

• with a known history of a severe (CTC grade 3/4) hypersensitivity reaction to agents containing Cremophor® EL or its derivatives such as polyoxyethylated castor oil

• who have a baseline neutrophil count <1500 cells/mm3 or a platelet count <100,000 cells/mm3

Peripheral neuropathy

-Peripheral neuropathy was common. Patients treated with IXEMPRA should be monitored for symptoms of neuropathy, such as burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, or neuropathic pain-Neuropathy occurred early during treatment; ~75% of new onset or worsening neuropathy occurred during the first 3 cycles. Patients experiencing new or worsening peripheral neuropathy may require changes in the dose or discontinuation of IXEMPRA

-Neuropathy was the most frequent cause of treatment discontinuation due to drug toxicity. Caution should be used when treating patients with diabetes mellitus or preexisting peripheral neuropathy

Myelosuppression

-Myelosuppression is dose-dependent and primarily manifested as neutropenia.

-Patients should be monitored for myelosuppression; frequent peripheral blood cell counts are recommended for all patients receiving IXEMPRA

-Patients who experience severe neutropenia or thrombocytopenia should have their dose reduced. Neutropenia-related deaths occurred in 1.9% of 414 patients with normal hepatic function or mild hepatic impairment treated with IXEMPRA in combination with capecitabine. Neutropenia-related death occurred in 0.4% of 240 patients with IXEMPRA as monotherapy

Hypersensitivity reaction

-Premedicate with an H1 and an H2 antagonist approximately 1 hour before IXEMPRA infusion and observe for hypersensitivity reactions (eg, flushing, rash, dyspnea, and bronchospasm)

-In case of severe hypersensitivity reactions, infusion of IXEMPRA should be stopped and aggressive supportive treatment (eg, epinephrine, corticosteroids) started

-Patients who experience a hypersensitivity reaction in one cycle of IXEMPRA must be premedicated in subsequent cycles with a corticosteroid in addition to the H1 and H2 antagonists, and extension of the infusion time should be considered

Pregnancy

-Women should be advised not to become pregnant when taking IXEMPRA. If this drug is used during pregnancy or the patient becomes pregnant, the patient should be apprised of the potential hazard to the fetus

Cardiac adverse reactions

-Caution should be exercised in patients with a history of cardiac disease. Discontinuation of IXEMPRA should be considered in patients who develop cardiac ischemia or impaired cardiac function due to reports of cardiovascular adverse reactions (eg, myocardial ischemia, supraventricular arrhythmia, and ventricular dysfunction). The frequency of cardiac adverse reactions (myocardial ischemia and ventricular dysfunction) was higher in the IXEMPRA in combination with capecitabine (1.9%) than in the capecitabine alone(0.3%) treatment group

Potential for cognitive impairment from excipients

-IXEMPRA contains dehydrated alcohol USP. Consideration should be given to the possibility of central nervous system and other effects of alcohol

Adverse reactions

-The most common adverse reactions (≥20%) reported by patients receiving IXEMPRA were peripheral sensory neuropathy, fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting, stomatitis/mucositis, diarrhea, and musculoskeletal pain. The following additional events occurred in ≥20% in combination treatment: palmar-plantar erythrodysesthesia (hand-foot) syndrome, anorexia, abdominal pain, nail disorder, and constipation. Drug-associated hematologic abnormalities (>40%) include neutropenia, leukopenia, anemia, and thrombocytopenia

Cremophor is a registered trademark of BASF AG

AST = aspartate aminotransferase; ALT = alanine aminotransferase;
ULN = upper limit of normal; CTC = common terminology criteria.

The full Prescribing Information, including Boxed Warning regarding hepatic impairment, is available at www.bms.com.

ERBITUX® (cetuximab) INDICATIONS & IMPORTANT SAFETY INFORMATION Including BOXED WARNING

INDICATIONS

Head and Neck Cancer

  • ERBITUX® (cetuximab), in combination with radiation therapy, is indicated for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck
  • ERBITUX, as a single agent, is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed

Colorectal Cancer

  • ERBITUX, as a single agent, is indicated for the treatment of EGFR-expressing metastatic colorectal cancer after failure of both irinotecan- and oxaliplatin-based regimens. ERBITUX, as a single agent, is also indicated for the treatment of EGFR-expressing metastatic colorectal cancer in patients who are intolerant to irinotecan-based regimens
  • ERBITUX, in combination with irinotecan, is indicated for the treatment of EGFR-expressing metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. The effectiveness of ERBITUX in combination with irinotecan is based on objective response rates. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with ERBITUX in combination with irinotecan for the treatment of EGFR-expressing metastatic colorectal carcinoma
  • Retrospective subset analyses of metastatic or advanced colorectal cancer trials have not shown a treatment benefit for ERBITUX in patients whose tumors had K-ras mutations in codon 12 or 13. Use of ERBITUX is not recommended for the treatment of colorectal cancer with these mutations

IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNINGS

Infusion Reactions

  • Grade 3/4 infusion reactions occurred in approximately 3% of patients receiving ERBITUX® (cetuximab) in clinical trials, with fatal outcome reported in less than 1 in 1000
    • Serious infusion reactions, requiring medical intervention and immediate, permanent discontinuation of ERBITUX, included rapid onset of airway obstruction (bronchospasm, stridor, hoarseness), hypotension, shock, loss of consciousness, myocardial infarction, and/or cardiac arrest
    • Immediately interrupt and permanently discontinue ERBITUX infusions for serious infusion reactions
  • Most (90%) of the severe infusion reactions were associated with the first infusion of ERBITUX despite premedication with antihistamines
    • Caution must be exercised with every ERBITUX infusion, as there were patients who experienced their first severe infusion reaction during later infusions
    • Monitor patients for 1 hour following ERBITUX infusions in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (eg, epinephrine, corticosteroids, intravenous antihistamines, bronchodilators, and oxygen). Longer observation periods may be required in patients who require treatment for infusion reactions

Cardiopulmonary Arrest

  • Cardiopulmonary arrest and/or sudden death occurred in 4 (2%) of 208 patients with squamous cell carcinoma of the head and neck treated with radiation therapy and ERBITUX, as compared to none of 212 patients treated with radiation therapy alone. In three patients with prior history of coronary artery disease, death occurred 27, 32, and 43 days after the last dose of ERBITUX. One patient with no prior history of coronary artery disease died one day after the last dose of ERBITUX.
  • Carefully consider the use of ERBITUX in combination with radiation therapy in head and neck cancer patients with a history of coronary artery disease, congestive heart failure or arrhythmias in light of these risks
    • Closely monitor serum electrolytes including serum magnesium, potassium, and calcium during and after ERBITUX therapy

Pulmonary Toxicity

  • Interstitial lung disease (ILD), which was fatal in one case, occurred in 4 of 1570 (<0.5%) patients receiving ERBITUX in clinical trials. Interrupt ERBITUX for acute onset or worsening of pulmonary symptoms. Permanently discontinue ERBITUX where ILD is confirmed

Dermatologic Toxicities

  • In clinical studies of ERBITUX, dermatologic toxicities, including acneiform rash, skin drying and fissuring, paronychial inflammation, infectious sequelae (eg, S. aureus sepsis, abscess formation, cellulitis, blepharitis, conjunctivitis, keratitis, cheilitis), and hypertrichosis, occurred in patients receiving ERBITUX therapy. Acneiform rash occurred in 76-88% of 1373 patients receiving ERBITUX in clinical trials. Severe acneiform rash occurred in 1-17% of patients
  • Acneiform rash usually developed within the first two weeks of therapy and resolved in a majority of the patients after cessation of treatment, although in nearly half, the event continued beyond 28 days
    • Monitor patients receiving ERBITUX for dermatologic toxicities and infectious sequelae
    • Sun exposure may exacerbate these effects

ERBITUX Plus Radiation Therapy and Cisplatin

  • The safety of ERBITUX in combination with radiation therapy and cisplatin has not been established
    • Death and serious cardiotoxicity were observed in a single-arm trial with ERBITUX, radiation therapy, and cisplatin (100 mg/m2) in patients with locally advanced squamous cell carcinoma of the head and neck
    • Two of 21 patients died, one as a result of pneumonia and one of an unknown cause
    • Four patients discontinued treatment due to adverse events. Two of these discontinuations were due to cardiac events

Electrolyte Depletion

  • Hypomagnesemia occurred in 55% (199/365) of patients receiving ERBITUX and was severe (NCI CTC grades 3 & 4) in 6-17%. The onset of hypomagnesemia and accompanying electrolyte abnormalities occurred days to months after initiation of ERBITUX therapy
    • Monitor patients periodically for hypomagnesemia, hypocalcemia and hypokalemia, during, and for at least 8 weeks following the completion of, ERBITUX therapy
    • Replete electrolytes as necessary

Late Radiation Toxicities

  • The overall incidence of late radiation toxicities (any grade) was higher with ERBITUX in combination with radiation therapy compared with radiation therapy alone. The following sites were affected: salivary glands (65%/56%), larynx (52%/36%), subcutaneous tissue (49%/45%), mucous membranes (48%/39%), esophagus (44%/35%), and skin (42%/33%) in the ERBITUX and radiation versus radiation alone arms, respectively
    • The incidence of grade 3 or 4 late radiation toxicities were similar between the radiation therapy alone and the ERBITUX plus radiation therapy arms

Pregnancy and Nursing

  • In women of childbearing potential, appropriate contraceptive measures must be used during treatment with ERBITUX and for 6 months following the last dose of ERBITUX. ERBITUX may be transmitted from the mother to the developing fetus, and has the potential to cause fetal harm when administered to pregnant women. ERBITUX should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus
  • It is not known whether ERBITUX is secreted in human milk. IgG antibodies, such as ERBITUX, can be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from ERBITUX, a decision should be made whether to discontinue nursing or to discontinue ERBITUX, taking into account the importance of ERBITUX to the mother. If nursing is interrupted,based on the mean half-life of cetuximab, nursing should not be resumed earlier than 60 days following the last dose of ERBITUX

Adverse Events

  • The most serious adverse reactions associated with ERBITUX across all studies were infusion reactions, cardiopulmonary arrest, dermatologic toxicity and radiation dermatitis, sepsis, renal failure, interstitial lung disease, and pulmonary embolus
  • The most common adverse reactions associated with ERBITUX (incidence ≥25%) are cutaneous adverse reactions (including rash, pruritus, and nail changes), headache, diarrhea, and infection
  • The most frequent adverse events seen in patients with carcinomas of the head and neck receiving ERBITUX in combination with radiation therapy (n=208) versus radiation alone (n=212) (incidence≥50%) were acneiform rash (87%/10%), radiation dermatitis (86%/90%), weight loss (84%/72%), and asthenia (56%/49%). The most common grade 3/4 adverse events for ERBITUX in combination with radiation therapy (≥10%) vs radiation alone included: radiation dermatitis (23%/18%), acneiform rash (17%/1%), and weight loss (11%/7%)
  • The most frequent adverse events seen in patients with metastatic colorectal cancer (n=288) in the ERBITUX + best supportive care arm (incidence ≥50%) were fatigue (89%), rash/desquamation (89%), abdominal pain (59%), and pain-other (51%). The most common grade 3/4 adverse events (≥10%) included: fatigue (33%), pain-other (16%), dyspnea (16%), abdominal pain (14%), infection without neutropenia (13%), rash/desquamation (12%), and other-gastrointestinal (10%)
  • The most frequent adverse events seen in patients with metastatic colorectal cancer (n=354) treated with ERBITUX plus irinotecan in clinical trials (incidence ≥50%) were acneiform rash (88%), asthenia/malaise (73%), diarrhea (72%), and nausea (55%). The most common grade 3/4 adverse events (≥ 10%) included: diarrhea (22%), leukopenia (17%), asthenia/malaise (16%), and acneiform rash (14%)

Please see Important Safety Information and U.S. Complete Product Information including Boxed WARNINGS about allergic reactions and heart attack.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit www.bms.com, or follow us on Twitter at http://twitter.com/bmsnews.

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the investigational compounds described in this release will receive regulatory approvals or, if approved, that they will become commercially successful. There is also no guarantee that the investigational uses of currently-approved products described in this release will lead to additional approved indications for such products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

* Gleevec® is a registered trademark of Novartis AG



CONTACT:

Bristol-Myers Squibb
Media:
Sarah Koenig, 609-252-4145
[email protected]
or
Investors:
John Elicker, 609-252-4611
[email protected]

KEYWORDS:   United States  North America  New Jersey

INDUSTRY KEYWORDS:   Health  Clinical Trials  Oncology  Pharmaceutical

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